Genetic control of ATGL-mediated lipolysis modulates adipose triglyceride stores in leptin-deficient mice

Genevieve Marcelin, Shun Mei Liu, Xiaosong Li, Gary J. Schwartz, Streamson Chua

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Dissecting the genetics of complex traits such as obesity allows the identification of causal genes for disease. Here, we show that the BALB/c mouse strain carries genetic variants that confer resistance to obesity induced by leptindefi ciency or a high-fat diet (HFD). We set out to identify the physiological and genetic bases underlying this phenotype. When compared with C57BL6/J ob/ob mice (B6), BALB/c ob/ob mice exhibited decreased food intake, increased thermogenic capacity, and improved fat catabolism, each of which can potentially modify obesity. Interestingly, analysis of F1 ob/ob (progeny of B6 ob/+ x BALB/c ob+ ) mice revealed that obesity resistance in BALB/c ob/ob mice principally relied upon improved fat mobilization. This was mechanistically explained by increased adipose triglyceride lipase (ATGL) content in adipocytes, along with increased lipolysis and fatty acid oxidation. We conducted a genomewide scan and defined a quantitative trait locus (QTL) on chromosome 2. BALB/c alleles on chromosome 2 not only associated with the obesity resistance phenotype but also supported increased ATGL content in adipose tissue. In summary, our study provides evidence that leptin-independent control of adipocyte lipolysis rates directly modifies the balance of macronutrient handling and is sufficient to regulate fat mass in the absence of alterations in food intake and energy expenditure.

Original languageEnglish (US)
Pages (from-to)964-972
Number of pages9
JournalJournal of Lipid Research
Issue number5
StatePublished - May 2012


  • Adipocytes
  • Adipose triglyceride lipase
  • Obesity
  • Quantitative trait locus

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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